Given the allergic reaction caused by mangoes, nonthermal food technologies for allergenicity reduction are urgently desired. This study aimed to assess the impact of kombucha fermentation on the allergenicity of mangoes. The total proteins, soluble proteins, peptides, amino acid nitrogen, the SDS-PAGE profiles of the protein extracts, and immunoreactivity of the sediment and supernatant were measured in two fermentation systems (juices and pieces fermentation). Throughout the fermentation, the pH decreased from about 4.6 to about 3.6, and the dissolved oxygen reduced about 50% on average. However, the protein degradation and sensitization reduction of mangoes were different between the two fermentation systems. In juices fermentation, there was a drop in proteins and peptides but an increase in amino acids, due to the conversion of proteins and peptides into amino acids both in the supernatant and sediment. The allergenicity decreased both in the solid and liquid phases of juices fermentation. In pieces fermentation, proteins and peptides were decreased in the solid phase but increased in the liquid phase. This was due to the fact that proteins and peptides were partly transported into the culture liquid, resulting in a decrease of allergenicity in fruit pieces and an increase in culture liquid. The principal component analysis results showed that the fermentation type had significant effects on the protein degradation and sensitization reduction, while mango variety had no significant effect. These results demonstrate that kombucha fermentation can reduce the allergenicity of mangoes, and it is more effective in juices fermentation than in pieces fermentation. The present study provides a theoretical basis for developing hypoallergenic mango products.